title: p62/SQSTM1 involved in cisplatin resistance in human ovarian cancer cells by clearing ubiquitinated proteins.
abstract: Mechanisms of cisplatin resistance in cancer cells are not fully understood. Here, we show a critical role for the ubiquitin-binding protein p62/SQSTM1 in cisplatin resistance in human ovarian cancer cells (HOCCs). Specifically, we found that cisplatin-resistant SKOV3/DDP cells express much higher levels of p62 than do cisplatin-sensitive SKOV3 cells. The protein p62 binds ubiquitinated proteins for transport to autophagic degradation, reducing apoptosis induced by endoplasmic reticulum (ER) stress in SKOV3/DDP cells. Knockdown of p62 or inhibition of autophagy using 3-methyladenine resensitises SKOV3/DDP cells to cisplatin. Collectively, our data indicate that p62 acts as a receptor or adaptor for autophagic degradation of ubiquitinated proteins, and plays an important role in preventing ER stress-induced apoptosis, leading to cisplatin resistance in HOCCs.
authors.affiliation: Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, PR China.
authors.forename: Huimei
authors.initials: H
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Kang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Haowei
authors.initials: H
authors.lastname: Yi
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xiang
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Liankun
authors.initials: L
authors.lastname: Sun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D001343:Autophagy; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000737:chemistry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin; D057149:Ubiquitinated Proteins; D002945:Cisplatin